Elevated Acute Phase Reactants Research Articles

#2698 Regression of amyloid deposits after treatment with tocilizumab

Abstract Background and Aims AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) is effective in suppressing inflammation, normalizing serum amyloid A protein levels and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Results We report a case of AA amyloidosis secondary to chronic arthritis in a 61-year-old woman referred to our hospital in 2011 due to oligoarthritis of the knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate and nephrotic-range proteinuria were found. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both (Fig. 1A, B). Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition (Fig. 2). Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria (Fig. 3) and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits (Fig. 1C, D) and right knee MRI was normal, without evidence of amyloid synovitis (Fig. 4). Eight years later, the patient continues treatment with tocilizumab and remains clinically stable, with no evidence of recurrence. Literature review: The efficacy of tocilizumab has been described mainly in patients with rheumatoid arthritis, but also in AA amyloidosis secondary to systemic juvenile idiopathic arthritis, familial Mediterranean fever, psoriatic arthritis, ankylosing spondylitis, Still's disease, Muckle-Wells syndrome, Behçet syndrome, polyarteritis nodosa and Takayasu arteritis. Some of the studies report long-term effectiveness of up to 9 years. In 11 case reports of patients with AA amyloidosis treated with tocilizumab, a follow-up biopsy was performed and a reduction or disappearance of the deposits was also observed. Lane et al. analyzed pre- and on-treatment serial scintigraphy scans in 20 patients with AA amyloidosis, showing that AA amyloid deposits either regressed or did not increase whilst on tocilizumab. We have not identified any study demonstrating the disappearance of amyloid arthropathy in MR images. Conclusion Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. Long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure of this disease.

#2460 Haemodialysis-related periarticular calcifications as cause of recurrent severe inflammatory state

Abstract Background and Aims End stage chronic kidney disease (CKD) and haemodialysis (HD) are associated with disturbances in mineral and bone turnover ultimately leading to chronic kidney disease–mineral and bone disorder (CKD-MBD), which affects more than 90 % of patients with stage 5D CKD. The primary changes observed in CKD–MBD involve elevated phosphorus levels, decreased calcium levels, insufficient serum vitamin D, and heightened release of parathyroid hormone from the parathyroid glands, leading to secondary hyperparathyroidism. CKD-MBD leads to vascular calcification, increasing cardiovascular risk. There is also a correlation between abnormal bone remodeling activity in CKD-MBD and the likelihood of calcification in soft tissues. In rare instances, profound calcification occurs in periarticular tissues, resulting in severe inflammation and manifesting as systemic disease with articular involvement clinically. The objective of this case report is to demonstrate a recurrent inflammatory condition caused by severe periarticular calcification in a patient on HD. Case report We present a case of a middle-aged white male diagnosed with hypertension, hypercholesterolemia, chronic obstructive pulmonary disease, hepatitis C, and end-stage renal disease caused by hydronephrosis. He was undergoing HD since July 2020. From summer 2021 the patient experienced recurrent fever and arthralgias in the hips, elbows, and shoulders. Frequent acute hospitalizations were needed due to recurring fevers and severe inflammatory response with markedly elevated acute phase reactants (CRP was repeatedly >200 mg/l), raising suspicion of infection. Laboratory and imaging tests however showed no clear signs of infection, and antibiotic therapy was ineffective. An x-ray of the right AC-joint showed multiple periarticular calcifications dorsally from the AC-joint. Later, due to severe pain and swelling an MRI-scan of right elbow joint was conducted, revealing an osteomyelitis-suspect finding of the olecranon, and olecranon bursitis. No bacteria were detected in the punctate of olecranon bursa. X-ray scans of the elbows revealed bilateral soft tissue calcification dorsally from the proximal ulna. The x-ray scan of the right shoulder revealed calcific expansion in the AC-joint area, leading to total destruction of the lateral part of the clavicle. MRI and CT scans showed severe periarticular calcification around AC- and glenohumeral joints without inflammatory involvement of the synovium. Bony erosions were observed due to the pressure of calcified tissue on the bone. Whole-body CT-scan showed no sites of infection but there was a periarticular calcification observed around the hip joints. A PET-CT scan of the whole body, neck, and upper extremities revealed no signs of malignancy or infections, but there was an increased uptake of 18F-fluorodeoxyglucose detected in several periarticular sites, indicating a multi-site inflammatory process resulting from severe periarticular calcifications. A dual-energy CT-scan of upper extremities was performed, excluding the accumulation of monosodium urate crystals. The cycle of multiple hospitalizations and antibacterial therapies was broken with the diagnosis of CKD and HD-related inflammatory periarticular calcification. Initially, the inflammation was addressed with high-dose glucocorticoids. However, the dose was successfully tapered during the first month of treatment, and the patient continued to do well on a maintenance dose of 5 mg/day of prednisolone. Subsequently, hospitalizations, antibiotics, or surgical procedures were no longer required. Conclusion Severe CKD and HD cause disturbances in mineral and bone metabolism, that can lead to periarticular calcification. Like in our presented case, multi-site calcifications may mimic infection or autoimmune rheumatoid conditions making the way to correct diagnosis cumbersome and costly. Imaging techniques help us distinguish periarticular deposits from inflammatory and infectious arthritis. In our case low-dose prednisolone effectively reduced inflammation, obviating hospitalizations and minimizing healthcare burden.

Blastocystis hominis -Associated Acute Appendicular Peritonitis in a 9-Year-Old Boy: A Case Report and a Comprehensive Review of the Literature.

Although Blastocystis sp. has been classically considered a commensal parasite with limited pathogenicity, recent studies suggest that its pathogenic potential is high. We report the case of a 9-year-old Spanish male who presented with peritonitis secondary to acute appendicitis with abundant intra-abdominal turbid-free fluid. A standard appendectomy was performed, and a sample of the fluid was taken for microbiological culture. Multimicrobial flora was isolated in peritoneal fluid culture. The antibiotic resistance study showed that all the microorganisms were sensitive to meropenem. On the 5th postoperative day, a control blood test showed relative eosinophilia and a persistently elevated C-reactive protein. A stool parasitological study showed abundant cysts morphologically compatible with Blastocystis hominis . The hematoxylin & eosin and Giemsa study identified abundant parasitic cysts in the appendix. The patient evolved favorably and is currently asymptomatic and under follow-up. Regarding acute appendicitis, there is only one report in the literature of peritonitis of appendiceal origin associated with Blastocystis sp. In conclusion, although infrequent, parasitosis should be considered as a potential etiological agent of acute appendicitis, even in nonendemic areas. Relative eosinophilia or persistently elevated acute phase reactants despite adequate antibiotic coverage should help to establish diagnostic suspicion.

Sweet Syndrome as a Herpetiform Mimic: A Diagnostic Challenge.

The authors present a singular case of Sweet syndrome (acute febrile neutrophilic dermatosis) manifesting with an unusual herpetiform clinical presentation, underscoring the imperative for its inclusion in differential diagnoses of herpetic infections. A 26-year-old female patient with a systemic lupus erythematosus history presented with facial edema, hyperthermia, cephalalgia, and polyarticular pain. Dermatological examination revealed clustered, vesicle-like papules on erythematous, edematous skin, mimicking herpetic infection. Elevated acute-phase reactants and urine anomalies were noted. Histopathology confirmed Sweet syndrome, characterized by superficial and deep neutrophilic dermatitis, karyorrhexis, and papillary dermal edema. The patient responded to corticosteroid therapy and a brief antibiotic course, resolving both systemic and cutaneous symptoms. This case is remarkable for its atypical herpetiform presentation, a clinical rarity in Sweet syndrome, challenging the conventional diagnostic process. It emphasizes the necessity of considering Sweet syndrome in differential diagnoses when encountering herpetiform lesions, particularly in patients with autoimmune backgrounds. This case contributes significantly to the understanding of Sweet syndrome's clinical variability and highlights the critical role of thorough clinicopathological evaluation in achieving accurate diagnosis in complex dermatological disorders.

Study of clinical profile of patients with acute coronary syndrome and the correlation of serum fibrinogen and grace score as a prognostic marker for predicting 3-month mortality

Introduction. Acute coronary syndrome (ACS), encompassing unstable angina, non-ST-segment eleva­tion myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), is a major global health concern due to its high morbidity and mortality. Research highlights a link between ACS and elevated acute phase reactants like C-reactive protein, emphasizing the role of inflammation and atherosclerosis. Serum fibrinogen, crucial in thrombus formation and an inflammatory marker, is significant in the coagu­lation process. This study investigates the predictive value of serum fibrinogen levels and the GRACE score for 3-month mortality in ACS patients. Aim. To examine the clinical profile of ACS patients and evaluate serum fibrinogen and GRACE score as prognostic markers for 3-month mortality. Methodology. A prospective observational study was conducted on 50 patients diagnosed with ACS at Saveetha Medical College Hospital. The study included adults over 18 with ACS, excluding those with severe comorbid conditions like end-stage liver disease or malignancy. Serum fibrinogen levels were measured at presentation and at 3 months using an automated coagulation analyzer. GRACE scores were calculated, and clinical assessments including ECG, cardiac markers, and ECHO were conducted. Data analysis involved IBM SPSS Statistics, utilizing descriptive statistics, t-tests, ANOVA, and Pearson's Correlation. Results. The study group had diverse demographics and a high prevalence of cardiovascular symptoms and comorbidities. The clinical profile of ACS showed a higher incidence of STEMI. Serum fibrinogen levels varied significantly across different Killip classes at presentation and at 3 months, with the highest levels in the more severe classes. Higher serum fibrinogen was linked to recurrent heart failure admissions and higher KILIPS class. However, there was no significant difference in fibrinogen levels between patients with and without interventions. The GRACE score was higher in STEMI patients, those with LV dysfunction, and correlated with higher serum fibrinogen. Lower FACIT F scores, indicating higher fatigue, were associated with higher fibrinogen levels and readmissions for heart failure. Conclusion. Higher serum fibrinogen levels and GRACE scores at presentation and at three months are indicators of severe myocardial infarction, increased heart failure readmission rates, and greater fatigue in ACS patients. These markers are valuable for evaluating morbidity in ACS and can aid in enhancing patient management strategies.

Limited Diagnostic and Prognostic Value of Routine Radiographs in Newly Presenting Arthritis Suspected of Rheumatoid Arthritis: A Retrospective Study.

Current recommendations suggest that patients with newly presenting arthritis suspected of rheumatoid arthritis (RA) should undergo routine radiographs of hands and feet (X-HF) as the presence of RA-associated erosions might be of diagnostic and prognostic value. Our objective was to investigate the prevalence, diagnostic, and prognostic value of RA-associated erosions seen on routine X-HF in a large, recent cohort of patients with newly presenting arthritis. A retrospective cohort study was performed between 2016 and 2019 in patients with newly presenting arthritis suspected of RA. Patients were included if arthritis was present at diagnosis, rheumatoid factor and anticitrullinated protein antibodies were measured, RA was noted in the differential diagnosis, and routine X-HF were conducted. Outcomes were the prevalence of one or more RA-associated erosion(s), and whether diagnostic or prognostic classification were changed by erosivity. Seronegative patients, patients without acute phase reactants, and patients with longer symptom duration were analyzed as subgroups. RA-associated erosions were found in 32 of 724 patients (4.4%, 95% confidence interval [95% CI] 3.1-6.2). Erosions led to a change of diagnostic classification in two patients (0.3%, 95% CI 0.01-1.1) and changed prognostic classification in three patients (0.4%, 95% CI 0.1-1.3). Seronegative patients and patients without elevated acute phase reactants had significantly lower prevalence of erosions (χ2 9.4, P = 0.002, χ2 6.5, P = 0.01). Longer symptom duration was not associated with a different prevalence of erosions (χ2 0.4, P = 0.81). The recommendation of conducting routine X-HF in patients with newly presenting arthritis suspected of RA might be reconsidered due to low prevalence of early erosive disease and lack of diagnostic and prognostic value.

Sarcoidosis with esophageal involvement: an uncommon clinical enigma.

We present the case of a 46-year-old male, a former smoker, with a medical history significant for morbid obesity grade III, hypothyroidism, hyperuricemia, and dyslipidemia. Four months ago, he was diagnosed with sarcoidosis involving mediastinal lymph nodes and is currently undergoing treatment with corticosteroids. The patient presented to the emergency department with persistent epigastric and thoracic pain lasting one week, accompanied by dysphagia and odynophagia intermittently. Laboratory tests showed elevated acute-phase reactants, with no other notable abnormalities. Chest X-ray revealed pre-existing mediastinal adenopathy. Despite an abdominal CT scan with contrast showing no significant findings, esophagogastroduodenoscopy revealed marked extrinsic compression of the esophagus between 25 and 32 cm from the dental arch, with less intensity distally. Although passage of the endoscope through this area caused significant pain, it did not hinder its advancement. A chest CT scan with oral contrast demonstrated filamentous narrowing of the esophagus in the middle third, along with concentric thickening of its walls and multiple paratracheal, parahilar, and periesophageal lymphadenopathies. Following a tapering regimen of corticosteroids, the patient was discharged with a clinical diagnosis of sarcoidosis with mediastinal and esophageal involvement secondary to extrinsic compression. Due to clinical improvement with the prescribed treatment, endoscopic ultrasound and biopsies to assess esophageal wall involvement were deemed unnecessary.

Raccoon eyes as a diagnostic key for suspected amyloidosis

Abstract A 74-year-old male was admitted to the emergency department with cutaneous lesions on his face resembling ‘raccoon eyes’, neck, and shoulders. He had also been experiencing asthenia, anorexia, weight loss, and symmetric polyarthritis for several months. Laboratory tests showed elevated acute phase reactants. Initial suspicion of amyloidosis led to further investigations, including serum and urine protein electrophoresis and immunofixation, resulting in a diagnosis of primary amyloidosis associated with IgG multiple myeloma. The patient began conventional treatment for multiple myeloma. However, he died to another condition (bacterial pneumonia) two months later.

An overlooked cause of hepatitis and thrombocytopenia with clinico-biochemical discrepancy: A case of infectious mononucleosis

A 22-year-old male was admitted to the outpatient clinic with fatigue, fever, and a sore throat. High transaminase levels, moderate thrombocytopenia, and elevated acute phase reactants were detected ten times. Ultrasound imaging revealed hepatosplenomegaly and a peripheral blood smear showed Downey cells. Epstein-Barr virus (EBV) infection was considered the definite diagnosis, and EBV serology was performed. His mild clinic improved to normal within days, but the patient's clinical progression and laboratory findings were incompatible. Laboratory results were on the extreme side, while the clinic was mildly deteriorating. EBV viral capsid antigen IgM was high, supporting the initial diagnosis. Biochemical normalization followed clinical improvement many days later. Clinicians should know that EBV infection may be mild, while laboratory results illustrate extreme findings.

Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib

BackgroundAicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression.Case presentationWe describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6.ConclusionsRuxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.

Escroto agudo en el lactante

Acute scrotum consists of testicular pain associated with local inflammatory signs and is very unsual in neonates and infants. We present a case of a 2-month-old infant with right scrotal swelling and erythema of 48 hours' evolution. Peak fever in the emergency department. On examination, the teste was painful on palpation, with cremasteric reflex present. Testicular ultrasound showed right orchiepididymitis with associated hydrocele. Laboratory tests show leukocytosis, neutrophilia and minimal elevation of acute phase reactants. Urine culture isolated Escherichia coli. He received antibiotherapy for 2 weeks with good evolution. Orchiepididymitis is an acute inflammation of the testicle and epididymis, and it is a very rare pathology in neonates and infants. Haematogenous dissemination is the most frequent cause in this age group, with E. coli being the most frequently isolated germ. Therefore, in neonates and infants with orchiepididymitis, considering the risk of associated bacteraemia, it is essential to optimize the diagnosis by including a complete sepsis study together with Doppler ultrasound and the early initiation of empirical antibiotherapy.

What General Neurologists Should Know about Autoinflammatory Syndromes?

Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

Cutaneous findings and treatments in deficiency of interleukin-36 receptor antagonist (DITRA): A review of the literature.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

Case report: Diagnosis and resolution of hepatic abscess in a neonate

BACKGROUND: Hepatic abscesses in the neonatal age can be caused by multiple etiologies and their variability in clinical presentation makes their diagnosis difficult. The incidence of infectious liver abscesses is low, however, their mortality is high and their timely diagnosis and early resolution are essential to improve prognosis and life expectancy, since therapeutic management is the cause of prolonged hospitalization due to the administration of long-lasting intravenous antimicrobials. The following is a case report of a neonatal patient with this pathology. CLINICAL REPORT: neonatal patient born by cesarean section, 38 weeks of gestation, male, admitted to the neonatology department due to the need for mechanical ventilation; with umbilical catheters for 72 hours. At 48 hours of life, he presented febrile peaks and elevation of acute phase reactants, later, abdominal distension, feeding intolerance and hepatomegaly, so antibiotic therapy was administered with suspicion of septic ileus. Due to persistent hepatomegaly, an abdominal ultrasound was performed in which cystic images were observed at the hepatic level. EVOLUTION: after the diagnosis of liver abscesses, it was decided to maintain antibiotic therapy with Meropenem and Vancomycin. Due to persistence of the abscesses despite treatment, surgical drainage was required on two occasions, the first at day 30 of life, and the second at 47 days of life. The newborn received, from the onset of symptoms and clinical symptoms, a total of 60 days of Meropenem and 48 days of Vancomycin, with complete resolution of the lesions after 68 days of hospitalization. CONCLUSION: Hepatic abscesses are rare in the neonatal age, of bacterial origin in most cases, related to hematic propagation due to umbilical catheterization. The pathology involves long hospitalizations and long-term antibiotic therapy; however, its prognosis is good with early diagnosis and timely treatment.

"Usefulness of the Acute Phase Reactants (APR) Score [Part 4]: Transient Elevation of Acute Phase Reactants in the Early Neonatal Period is Due to Inflammation Not Infection"

"Usefulness of the Acute Phase Reactants (APR) Score [Part 4]: Transient Elevation of Acute Phase Reactants in the Early Neonatal Period is Due to Inflammation Not Infection"

Post-Cardiac Injury Syndrome (Dressler Syndrome) Following Atrial Septal Defect (ASD) Repair: a Case Report

Dressler syndrome is a type of secondary pericarditis that can be accompanied by pleural effusion or pericardial effusion resulting from injury of the pericardium or heart tissue. A 33-year-old male was admitted to the emergency department with pleuritic chest pain radiating to both shoulders and fever. Two months before the admission, the patient underwent traditional open-heart surgery with median sternotomy and pericardiectomy for atrial septal defect (ASD) closure. Blood tests showed elevated acute phase reactants (leukocytosis, high erythrocyte sedimentation rate, and C-reactive protein). Left-sided pleural effusion was revealed on chest CT scan. Diagnosis of Dressler syndrome was established. The patient’s pleuritic chest pain and shoulder pain improved clinically with a short course of colchicine. Although Dressler syndrome is rarely seen, it should be considered in the differential diagnosis of pleuritic chest pain. Special attention should be paid to Dressler’s syndrome because pericarditis can develop following cardiac surgery.

Pyoderma gangrenosum associated with rheumatoid arthritis mimicking vasculitis

Pyoderma gangrenosum is a rare neutrophilic dermatosis characterized by painful, rapidly progressing necrotic ulcers. Although PG has been reported in association with various autoimmune diseases, its coexistence with rheumatoid arthritis (RA) mimicking vasculitis is uncommon. We present a case report of a 75-year-old female with a longstanding history of RA who developed ulcerative skin lesions that initially presented as vasculitis. She presented with new-onset painful, ulcerative skin lesion on the lower extremity, accompanied by malaise. Physical examination revealed asymmetric, deep necrotic ulcers with undermined borders. Laboratory investigations showed elevated acute phase reactants and negative rheumatoid factor. Skin biopsy demonstrated neutrophilic infiltration, confirming the diagnosis of PG. Further investigations, including imaging studies and vasculitis-specific laboratory tests, were negative, ruling out vasculitis. The patient was managed with systemic corticosteroids and immunosuppressive therapy, resulting in significant improvement of skin lesions. This case highlights the importance of considering PG as a potential differential diagnosis in patients with RA presenting with ulcerative skin lesions resembling vasculitis.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Reasons for requesting an interferon gamma release test from internal medicine and rheumatology clinics and evaluation of the results

Background/Aim: Tuberculosis is a disease involving many systems, such as the lung, gastrointestinal system, genitourinary system, etc. Detecting this disease in its latency significantly reduces the morbidity and mortality associated with tuberculosis. One of the tests used in latent TB screening is the interferon gamma release test. In rheumatology practices, it is routinely used to screen for latent tuberculosis infections before treatment with biological agents and Janus kinase (JAK) inhibitors, and it can also be used to exclude tuberculosis infection in clinical practice. In our study, we aimed to evaluate the reasons for requesting interferon gamma release tests and the results of this test in patients who requested it. Methods: Patients admitted to internal medicine and rheumatology outpatient clinics were retrospectively screened within the retrospective cohort study. In total, 364 patients who requested interferon gamma release testing were included in the study. Nine patients with unclear test results were excluded. Laboratory results, demographic data, reasons for requesting the interferon gamma release test, and results were evaluated. Results: The interferon gamma release test was requested by 355 patients. Of these, 266 patients (74.9%) asked for latent tuberculosis screening before treatment with biological agents and JAK inhibitors. This was followed by patients with peripheral lymphadenopathy-lung nodules, patients with unexplained elevated acute phase reactants, and patients with constitutional symptoms, respectively. Ten out of 107 patients (9.3%) had an active tuberculosis infection, while six out of ten patients (60%) had pulmonary tuberculosis, and four (40%) had extrapulmonary tuberculosis. Conclusion: The most common reason for requesting the interferon gamma release test in internal medicine and rheumatology clinics was screening for latent tuberculosis before treatment with biologic agents and JAK inhibitors. In internal medicine, it has been observed that this test can also be requested by patients with constitutional symptoms, unexplained elevated acute phase reactants, and a preliminary diagnosis of tuberculosis in order to rule out or strengthen the preliminary diagnosis.

Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia.

In gout, hyperuricemia promotes urate crystal deposition, which stimulates the NLRP3 inflammasome and interleukin-1β (IL-1β)-mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia-independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis in a young female patient with normouricemia diagnosed as having sufficient and weighted classification criteria for gout according to the American College of Rheumatology (ACR)/EULAR gout classification criteria (the proband). We conducted whole-genome sequencing, quantitative proteomics, whole-blood RNA-sequencing analysis using serum samples from the proband. We used a mouse model of IL-1β-induced knee synovitis to characterize proband candidate genes, biomarkers, and pathogenic mechanisms of gout. Lubricin level was attenuated in human proband serum and associated with elevated acute-phase reactants and inflammatory whole-blood transcripts and transcriptional pathways. The proband had predicted damaging gene variants of NLRP3 and of inter-α trypsin inhibitor heavy chain 3, an inhibitor of lubricin-degrading cathepsin G. Changes in the proband's serum protein interactome network supported enhanced lubricin degradation, with cathepsin G activity increased relative to its inhibitors, SERPINB6 and thrombospondin 1. Activation of Toll-like receptor 2 (TLR-2) suppressed levels of lubricin mRNA and lubricin release in cultured human synovial fibroblasts (P < 0.01). Lubricin blunted urate crystal precipitation and IL-1β induction of xanthine oxidase and urate in cultured macrophages (P < 0.001). In lubricin-deficient mice, injection of IL-1β in knees increased xanthine oxidase-positive synovial resident M1 macrophages (P < 0.05). Our findings linked normouricemic erosive gout to attenuated lubricin, with impaired control of cathepsin G activity, compounded by deleterious NLRP3 variants. Lubricin suppressed monosodium urate crystallization and blunted IL-1β-induced increases in xanthine oxidase and urate in macrophages. The collective activities of articular lubricin that could limit incident and erosive gouty arthritis independently of hyperuricemia are subject to disruption by inflammation, activated cathepsin G, and synovial fibroblast TLR-2 signaling.